Autonomous, ambulatory analyte monitor or drug delivery device

• US 7,004,928 B2
• Filed: 04/23/2002
• Issued: 02/28/2006
• Est. Priority Date: 02/08/2002
• Status: Active Grant

• Current Assignee: Intuity Medical, Inc.
• Original Assignee: Rosedale Medical Inc. (Intuity Medical, Inc.)
• Inventors: Zanzucchi, Peter John, McBride, Sterling Eduard, Moroney, Richard Morgan III, Aceti, John Gregory, Gregory, Christopher Carter
• Primary Examiner(s): Sirmons, Kevin C.
• Assistant Examiner(s): Han, Mark K
• Application Number:
  US10/131,268
• Publication Number:
  US 20030153900A1
• Time in Patent Office: 1,407 Days
• Field of Search: 604/27, 604/36, 604/48, 604/93.01, 604/187, 604/191, 604/192, 604/197, 604/239, 600345-361, 600/573, 600/575, 600/576, 600/578, 600/579, 600/583, 606/167, 606/181, 606/182, 606/183, 606/185, 606/186
• US Class Current: 604/191
• CPC Class Codes: A61B 2560/0412 Low-profile patch shaped housings
• CPC Class Codes: A61B 2560/0443 Modular apparatus
• CPC Class Codes: A61B 5/1411 by percutaneous method, e.g. by lancet
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150076 by heating
• CPC Class Codes: A61B 5/150213 Venting means
• CPC Class Codes: A61B 5/150389 Hollow piercing elements, e.g. canulas, needles, for piercing the skin
• CPC Class Codes: A61B 5/150503 Single-ended needles hollow piercing element tip design A61B5/150396, needle sets for catheters A61M25/06, needles for bringing media into the body A61M5/32
• CPC Class Codes: A61B 5/150526 Curved or bent needles
• CPC Class Codes: A61B 5/150755 Blood sample preparation for further analysis, e.g. by separating blood components or by mixing
• CPC Class Codes: A61B 5/15087 short range, e.g. between console and disposable using implanted devices A61B5/150877
• CPC Class Codes: A61B 5/150969 Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• CPC Class Codes: A61B 5/15109 Fully automatically triggered, i.e. the triggering does not require a deliberate action by the user, e.g. by contact with the patient's skin
• CPC Class Codes: A61B 5/15119 comprising shape memory alloys
• CPC Class Codes: A61B 5/15123 comprising magnets or solenoids
• CPC Class Codes: A61B 5/15146 : Devices loaded with multiple lancets simultaneously, e.g. for serial firing without reloading, for example by use of stocking means. multiple simultaneous cutting or piercing A61B5/150977
• CPC Class Codes: A61B 5/15153 : Multiple piercing elements stocked in a single compartment
• CPC Class Codes: A61B 5/15163 : Characterized by propelling the piercing element in an axial direction relative to the disc
• CPC Class Codes: A61B 5/155 : Devices specially adapted for continuous or multiple sampling, e.g. at predetermined intervals devices loaded with multiple lancets simultaneously A61B5/15146
• CPC Class Codes: A61B 5/157 : Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61B 5/681 : Wristwatch-type devices
• CPC Class Codes: A61B 5/6833 : Adhesive patches
• CPC Class Codes: A61M 2037/0023 : Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0038 : having a channel at the side surface
• CPC Class Codes: A61M 2209/088 : on the body
• CPC Class Codes: A61M 2230/201 : Glucose concentration
• CPC Class Codes: A61M 37/0015 : by using microneedles
• CPC Class Codes: G01N 33/491 : by separating the blood components G01N15/05 takes precedence

Abstract

The invention relates to analyte monitoring/drug (pharmaceutical agent) delivery device. The invention is suited for monitoring various blood constituents such as glucose. The device has a housing that at least partially encloses a plurality of microneedles disposed on a carrier and an electronics portion. Each microneedle is in fluid communication with a corresponding microchannel. Each microneedle is individually addressable. That is, each microneedle can be extended and retracted individually via an actuator. The electronics portion includes a processor and associated circuitry (e.g., memory, supporting electronics and the like), a motor or the like, a sensor, a power supply (e.g., battery) and optionally an interface. In general, the processor controls the operation of the device and is data communication with the actuator, motor, sensor and interface. The invention provides for autonomous operation, that is, without intervention of the user. The invention can optionally provide for calibration without intervention of the user. The invention can also provide for semi-continuous monitoring for day and night time. The invention can provide for up to four, or more, weeks of operation. The invention can provide for a device that is relative small in size, and therefore unobtrusive. The invention can also provide for device with remote control and interactive electronics. The invention may be also used for the delivery of various pharmaceutical agents including high potency drugs to minimize patient intervention and minimize discomfort.

Claims

1. An analyte monitoring device operable to draw a fluid sample from a subject, the device comprising:

a first plurality of microneedles,

a plurality of monitoring microchannels, wherein each of the first plurality of microneedles is at least intermittently in fluid communication with a corresponding monitoring microchannel, and

wherein each monitoring microchannel is associated with a reagent,

at least one detector associated with the monitoring microchannels, the detector comprising a CMOS imager;

at least one actuator operable to extend each microneedle to draw the fluid sample from the subject, and

a controller operable to initiate analyte testing of the fluid sample.

2. The device of claim 1 wherein the actuator is operable to extend at least one of the first plurality of microneedles omnidirectionally.

3. The device of claim 1 wherein each of the first plurality of microneedles has an internal diameter in the range of about 25 to 200 micrometers.

4. The device of claim 1 wherein each of the first plurality of microneedles is fabricated from at least one of metal, plastic, glass and crystal.

5. The device of claim 1 wherein each of the first plurality of microneedles has a distal end that is operable to penetrate into a skin surface to a maximum of about 2.5 mm.

6. The device of claim 1 wherein the fluid sample is substantially blood.

7. The device of claim 1 wherein each of the first plurality of microneedles is at least intermittently in fluid communication with a monitoring microchannel via a conduit.

8. The device of claim 1 wherein each monitoring microchannel is operable to store the fluid sample and accumulation of the fluid sample in the monitoring microchannel is entirely dependent on capillary forces.

9. The device of claim 1 wherein each of the monitoring microchannels has at least one internal surface that is at least partially coated with at least one insoluble material to enhance the capillary forces and minimize coagulation.

10. The device of claim 1 wherein the plurality of monitoring microchannels are fabricated in an array.

11. The device of claim 1 wherein the monitoring microchannels are fabricated in an array having approximately 50–

150 microchannels formed in a maximum diameter of approximately 5 cm.

12. The device of claim 1 wherein each of the first plurality of microneedles is dimensioned for volumes of fluid in the range of about 50–

500 nanoliters.

13. The device of claim 1 comprising a detector operable to determine when the fluid sample completely fills at least one monitoring microchannel such that the accumulation of the fluid sample with the associated microneedle may be terminated.

14. The device of claim 1 wherein at least one monitoring microchannel is in fluid communication with at least one reagent operable to assay for analytes selected from the group of (a) glucose, (b) cholesterol, (c) ethanol, (d) digoxin, (e) HDL cholesterol, (f) lithium, (g) sodium, (h) phenytoin, (i) therophylline, (j) cyclosporine, (k) cancer chemotheraphy drugs, (l) DNA, (m) RNA, (n) extended phenytonin sodium, (o) warfarin sodium, and (p) proteins derived from blood.

15. The device of claim 1 wherein at least two monitoring microchannels are associated with a single microneedle so that multiple assays can be performed using a single microneedle.

16. The device of claim 1 comprising a second plurality of microneedles and a plurality of calibration microchannels filled with calibration fluid, wherein at least one assay is initiated for calibration purposes.

17. The device of claim 1 comprising a third plurality of microneedles and a plurality of pharmaceutical agent delivery microchannels wherein each pharmaceutical agent. delivery microchannel is at least partially filled with a pharmaceutical agent.

18. The device of claim 17, wherein the analyte comprises an environmental toxin, and the pharmaceutical agent comprises an antidote to the toxin.

19. The device of claim 1 wherein at least one monitoring microchannel is sealed with a polymer.

20. The device of claim 1 wherein the controller is operable to initiate analyte testing based on a time schedule.

21. The device of claim 20 wherein the controller is operable to adjust the analyte testing time schedule.

22. The device of claim 1 wherein the controller is operable to couple to a portable computing device.

23. The device of claim 22 wherein the portable computing device is a PDA.

24. The device of claim 22 wherein at least one of the controller and the portable computing device is operable to select or modify times for analyte testing.

25. The device of claim 1 wherein the plurality of microneedles and plurality of monitoring microchannels are disposable.

26. The device of claim 1 wherein the controller and the actuator are reusable.

27. The device of claim 1 wherein the plurality of microneedles, plurality of monitoring microchannels, actuator and controller are portable.

28. The device of claim 1 comprising a heating source operable to heat at least one injection site prior to extending a microneedle.

29. The device of claim 28 wherein the heating source is an optical heating source.

30. The device of claim 1 comprising a housing at least partially coated with an adhesive operable to attach the housing to a surface, wherein the housing at least partially enclosing the plurality of microneedles and the monitoring microchannels.

31. The device of claim 1 comprising a generally disc shaped housing at least partially enclosing the plurality of microneedles and the monitoring microchannels.

32. The device of claim 1, wherein the imager comprises multiple pixels.

33. The device of claim 1, further comprising at least one emitter associated with the monitoring microchannels.

34. The device of claim 1, wherein the at least one detector is operable to detect the presence of blood in at least one of the monitoring microchannels prior to making a reading to determine concentration of the analyte in the sample.

35. A pharmaceutical agent delivery device operable to deliver a pharmaceutical agent to a subject, the device comprising:

a first plurality of microneedles,

a plurality of pharmaceutical agent delivery microchannels, wherein each of the first plurality of microneedles is at least intermittently in fluid communication with a corresponding pharmaceutical agent delivery microchannel, and wherein each pharmaceutical agent delivery microchannel is at least partially filled with a pharmaceutical agent,

at least one actuator operable to extend each microneedle to deliver the pharmaceutical agent to the subject, and

a controller operable to initiate delivery of the pharmaceutical agent.

36. The device of claim 35 wherein the actuator is operable to extend at least one of the first plurality of microneedles omnidirectionally.

37. The device of claim 35 wherein each of the first plurality of microneedles has an internal diameter in the range of about 25 to 200 micrometers.

38. The device of claim 35 wherein each of the first plurality of microneedles is fabricated from at least one of metal, plastic, glass and crystal.

39. The device of claim 35 wherein each of the first plurality of microneedles has a distal end that is operable to penetrate into a skin surface to a maximum of about 2.5 mm.

40. The device of claim 35 wherein each of the first plurality of microneedles is at least intermittently in fluid communication with a pharmaceutical agent delivery microchannel via a conduit.

41. The device of claim 35 wherein the delivery of the at least one pharmaceutical agent delivery is at least partially dependent on hydraulic forces.

42. The device of claim 35 wherein the plurality of pharmaceutical agent delivery microchannels are fabricated in an array.

43. The device of claim 35 wherein the pharmaceutical agent delivery microchannels are fabricated in an array having approximately 50–

150 microchannels formed in a maximum diameter of approximately 5 cm.

44. The device of claim 35 wherein each of the first plurality of microneedles is dimensioned for volumes of fluid in the range of about 50–

500 nanoliters.

45. The device of claim 35 comprising a detector operable to determine when the pharmaceutical agent delivery microchannel is empty.

46. The device of claim 35 comprising a third plurality of microneedles and a plurality of monitoring microchannels wherein each monitoring microchannel is associated with a reagent.

47. The device of claim 35 wherein at least one pharmaceutical agent delivery microchannel is sealed with a polymer.

48. The device of claim 35 wherein the controller is operable to initiate pharmaceutical agent delivery based on a time schedule.

49. The device of claim 48 wherein the controller is operable to adjust the pharmaceutical agent delivery time schedule.

50. The device of claim 35 wherein the controller is operable to couple to a portable computing device.

51. The device of claim 50 wherein the portable computing device is a PDA.

52. The device of claim 50 wherein at least one of the controller and the portable computing device is operable to select or modify times for analyte testing.

53. The device of claim 35 wherein the plurality of microneedles and plurality of pharmaceutical agent delivery microchannels are disposable.

54. The device of claim 35 wherein the controller and the actuator are reusable.

55. The device of claim 35 wherein the plurality of microneedles, plurality of pharmaceutical agent delivery microchannels, actuator and controller are portable.

56. The device of claim 35 comprising a heating source operable to heat at least one injection site prior to extending a microneedle.

57. The device of claim 56 wherein the heating source is an optical heating source.

58. The device of claim 35 comprising a housing at least partially coated with an adhesive operable to attach the housing to a surface, wherein the housing at least partially enclosing the plurality of microneedles and the pharmaceutical agent delivery microchannels.

59. The device of claim 35 comprising a generally disc shaped housing at least partially enclosing the plurality of microneedles and the pharmaceutical agent delivery microchannels.

60. In combination a device having an analyte monitor portion operable to draw a fluid sample from a subject and a pharmaceutical agent delivery portion operable to deliver a pharmaceutical agent to the subject, the device comprising:

a first plurality of microneedles,

a plurality of monitoring microchannels, wherein each of the first plurality of microneedles is at least intermittently in fluid communication with a corresponding monitoring microchannel, and

wherein each monitoring microchannel is associated with a reagent,

a second plurality of microneedles,

a plurality of pharmaceutical agent delivery microchannels, wherein each of the second plurality of microneedles is at least intermittently in fluid communication with a corresponding pharmaceutical agent delivery microchannel, and wherein each pharmaceutical agent delivery microchannel is at least partially filled with a pharmaceutical agent,

at least one actuator operable to extend each microneedle and one of draw the fluid sample from the subject and deliver the pharmaceutical agent to the subject, and

a controller operable to initiate analyte testing of the fluid sample and delivery of the pharmaceutical agent.

61. The device of claim 60 comprising a third plurality of microneedles and a plurality of calibration microchannels filled with calibration fluid, wherein at least one assay is initiated for calibration purposes.

62. A method for automated analyte monitoring comprising:

a) providing a first plurality of microneedles,

b) providing a plurality of monitoring microchannels, wherein each of the first plurality of microneedles is at least intermittently in fluid communication with a monitoring microchannel, and wherein each monitoring microchannel is associated with a reagent,

c) providing at least one detector associated with the monitoring microchannels, the detector comprising a CMOS imager;

d) sequentially extending a microneedle thereby obtaining a fluid sample from a subject,

e) initiating analyte testing of the fluid sample, and

f) providing a controller operable to automatically repeat steps c and d.

63. A method for automated pharmaceutical agent delivery comprising:

a) providing a first plurality of microneedles,

b) providing a plurality of pharmaceutical agent delivery microchannels, wherein each of the first plurality of microneedles is at least intermittently in fluid communication with a corresponding pharmaceutical agent delivery microchannel, and wherein each pharmaceutical agent delivery microchannel is at least partially filled with a pharmaceutical agent,

c) sequentially extending a microneedle thereby delivering the pharmaceutical agent to a subject,

d) providing a controller operable to automatically repeat step c.